Apparatus and method for increasing the sensitivity in the detection of optical coherence tomography and low coherence interferometry (“LCI”) signals by detecting a parallel set of spectral bands, each band being a unique combination of optical frequencies. The LCI broad bandwidth source is split into N spectral bands. The N spectral bands are individually detected and processed to provide an increase in the signal-to-noise ratio by a factor of N. Each spectral band is detected by a separate photo detector and amplified. For each spectral band the signal is band pass filtered around the signal band by analog electronics and digitized, or, alternatively, the signal may be digitized and band pass filtered in software. As a consequence, the shot noise contribution to the signal is reduced by a factor equal to the number of spectral bands. The signal remains the same. The reduction of the shot noise increases the dynamic range and sensitivity of the system.

Patent
   8054468
Priority
Jan 24 2003
Filed
Dec 13 2007
Issued
Nov 08 2011
Expiry
Oct 18 2023
Extension
267 days
Assg.orig
Entity
Large
16
557
all paid
1. An apparatus for optical imaging, comprising:
a) an interferometer;
b) a first arrangement providing at least one electro-magnetic radiation to the interferometer and a first signal, and generating a path length difference that is a fraction of a ranging depth of the interferometer;
c) a spectral separating second arrangement that receives a second signal from the interferometer and splits the second signal into a further signal having a plurality of optical frequencies, wherein the spectral separating unit obtains the second signal based on information provided by the first signal; and
d) a plurality of detectors, each detector configured to detect at least a portion of the optical frequencies received from the spectral separating second arrangement.
2. The apparatus according to claim 1, wherein the first arrangement comprises a fiber stretching arrangement.
3. The apparatus according to claim 1, wherein the first arrangement comprises a piezoelectric transducer configured to perform free space translational scanning.
4. The apparatus according to claim 1, wherein the first arrangement comprises a phase control optical delay line.
5. The apparatus according to claim 1, wherein the first arrangement scans over at least a fraction of the ranging depth equal to one over the number of detectors.
6. The apparatus according to claim 1, wherein the first arrangement further comprises a carrier frequency generator which is configured to facilitate carrier frequencies for the second signal.
7. The apparatus according to claim 1, wherein the first arrangement comprises an acoustic modulator.
8. The apparatus according to claim 1, wherein the first arrangement comprises an electro-optic modulator.
9. The apparatus according to claim 1, wherein the first arrangement comprises a phase control RSOD.
10. The apparatus according to claim 1, wherein the first arrangement produces a delay that has a distance that is less than a range of a sample arm.
11. The apparatus according to claim 1, wherein the spectral separating second arrangement comprises the at least one of (i) the addressable mirror array or (ii) the waveguide filter.
12. The apparatus according to claim 1, wherein the spectral separating second arrangement splits the signal into the bands.
13. The apparatus according to claim 1, wherein the detectors are provided in a form of a two-dimensional array.
14. The apparatus according to claim 1, wherein the sample is scanned in a series of simultaneous illuminations of substantially all areas of the sample.
15. The apparatus according to claim 1, wherein the spectral separating second arrangement comprises a polarization separating unit.
16. The apparatus according to claim 1, wherein the spectral separating second arrangement at least one of:
i. comprises at least one of (i) an addressable mirror array, or (ii) a waveguide filter, or
ii. splits the signal into a plurality of bands, whereby at least one of the bands comprises spectra that has a comb-like structure.
17. The apparatus according to claim 1, wherein the sample is scanned in a series of simultaneous illuminations of less than all of areas of the sample.
18. The apparatus according to claim 1, wherein the detectors include at least three detectors.

The present application is a divisional of U.S. Patent application Ser. No. 10/501,276, filed Jul. 9, 2004, which issued as U.S. Pat. No. 7,355,716 on Apr. 8, 2008, which is U.S. National Phase of International Application No. PCT/US03/02349 filed Jan. 24, 2003. This application also claims benefit of copending U.S. provisional patent application No. 60/351,904, filed Jan. 24, 2002, entitled APPARATUS AND METHOD FOR RANGING AND SHOT NOISE REDUCTION OF LOW COHERENCE INTERFEROMETRY (LCI) AND OPTICAL COHERENCE TOMOGRAPHY (OCT) SIGNALS BY PARALLEL DETECTION OF SPECTRAL BANDS, and copending U.S. application Ser. No. 10/136,813, filed Apr. 30, 2002, entitled METHOD AND APPARATUS FOR IMPROVING IMAGE CLARITY AND SENSITIVITY IN OPTICAL COHERENCE TOMOGRAPHY USING DYNAMIC FEEDBACK TO CONTROL FOCAL PROPERTIES AND COHERENCE GATING, both commonly assigned to the assignee of the present application. The disclosures of all these applications are incorporated herein by reference in their entireties.

The present invention relates to apparatus and a method for dramatically increasing the sensitivity in the detection of optical coherence tomography and low coherence interferometry signals by detecting a parallel set of spectral bands, each band being a unique combination of optical frequencies.

Two methods currently exist to implement depth ranging in turbid media. The first method is known as Low Coherence Interferometry (“LCI”). This method uses a scanning system to vary the reference arm length and acquire the interference signal at a detector and demodulating the fringe pattern to obtain the coherence envelope of the source cross correlation function. Optical coherence tomography (“OCT”) is a means for obtaining a two-dimensional image using LCI. OCT is described by Huang et al. in U.S. Pat. No. 5,321,501. Multiple variations on OCT have been patented, but, many suffer from less than optimal signal to noise ratio (“SNR”), resulting in non-optimal resolution, low imaging frame rates, and poor depth of penetration.

A second method for depth ranging in turbid media is known in the literature as spectral radar. In spectral radar the real part of the cross spectral density of sample and reference arm light is measured with a spectrometer. Depth profile information is encoded on the cross-spectral density modulation. Prior art for spectral radar is primarily found in the literature. U.S. Pat. No. 5,491,552 discloses a spectral radar invention which employs a variation of this technique. The use of spectral radar concepts to increase the signal to noise ratio of LCI and OCT have been described earlier. However, in this description, only the real part of the complex spectral density is measured and the method requires a large number of detector elements (˜2,000) to reach scan ranges on the order of a millimeter. It would be desirable to have a method that would allow for an arbitrary number of detector elements. Secondly, the previously described method uses a charge coupled device (“CCD”) to acquire the data, which requires a reduction of the reference arm power to approximately the same level as the sample arm power. As a result, large integration times are needed to achieve the SNR improvement. Since no carrier is generated, the 1/f noise will dominate the noise in this system. Power usage is a factor in such imaging techniques. For example in ophthalmic uses, only a certain number of milliwatts of power is tolerable before thermal damage can occur. Thus, boosting power is not feasible to increase SNR in such environments. It would be desirable to have a method of raising the SNR without appreciably increasing power requirements.

The present invention increases the SNR of LCI and OCT by splitting the LCI broad bandwidth source into N spectral bands. The N spectral bands are individually detected and processed to provide an increase in the SNR by a factor of N. This increase in SNR enables LCI or OCT imaging by a factor of N times faster, or alternatively allows imaging at the same speed with a source that has N times lower power. As a result, the present invention overcomes two of the most important shortcomings of LCI and OCT, i.e., source availability and scan speed. The factor N may reach more than 1,000, and allows construction of OCT and LCI systems that can be more than three orders of magnitude improved from OCT and LCI technology currently in practice.

The present invention enables a breakthrough in current data acquisition speeds and availability of sources for OCT. The shot noise reduction allows for much lower source powers, or much higher acquisition rates than current systems. Limitations in current data acquisition rates (approximately 4 frames/sec) are imposed by available source power. An increase in the sensitivity of the detection by a factor of 8 would allow real time imaging at a speed of 30 frames per second. An increase of the sensitivity by a factor of 1,000-2,000 would allow for the use of sources with much lower powers and higher spectral bandwidths which are readily available, cheaper to produce, and can generate broader bandwidths.

For ophthalmic applications of OCT, the efficient detection would allow for a significant increase of acquisition speed. The limitation in ophthalmic applications is the power that is allowed to enter the eye according to the ANSI standards (approximately 700 microwatts at 830 nm). Current data acquisition speed in ophthalmic applications is approximately 100-500 A-lines per second. The power efficient detection would allow for A-line acquisition rates on the order of 100,000 A-lines per second, or video rate imaging at 3,000 A-lines per image.

In summary, the present invention represents a greatly improved means for performing LCI and OCT, and as a result, would be of great interest to entities considering developing LCI and OCT diagnostic technologies for medical and non-medical applications.

Other features and advantages of the present invention will become apparent upon reading the following detailed description of embodiments of the invention, when taken in conjunction with the appended claims.

The invention is illustrated in the drawings in which like reference characters designate the same or similar parts throughout the figures of which:

FIG. 1 is a schematic view of a conventional system.

FIG. 2 is a schematic view of a preferred embodiment of the parallel detection scheme for LCI.

FIG. 3 is a schematic view of a system with one detector array according to one embodiment of the present invention.

FIG. 4 is a detail of a probe.

FIG. 5 is a schematic view of separating unit in combination with two integrating CCD arrays for detection of the dual-balanced wavelength demultiplexed signal.

FIG. 6 is a schematic view of a preferred embodiment of a standalone system

FIG. 7 is a schematic view showing spectral separating into 2 bands.

FIG. 8 is a schematic of spectral separating into 4 bands. The spectral resolution preferably used for each detector is twice as coarse as in the case of multiplexing into 2 bands.

FIG. 9 is a schematic view of using beam recombination to provide one dimension of interference information along one dimension of a two-dimensional detector array, while performing wavelength separating along the other dimension of the two dimensional array.

FIG. 10 is a schematic view of a phase tracking system according to one embodiment of the present invention.

FIG. 11 is a flowchart depicting the reconstruction of LCI or OCT signal from wavelength bands.

FIG. 12 is a schematic view of a spectral domain OCT interferometer design with a source combining the spectra of several superluminescent sources.

FIG. 13 is a schematic view of a system with a four detector array.

FIG. 14 is a graph of a typical interference patter as a function of path length difference between the sample arm and reference arm.

FIG. 15 is an embodiment of a phase tracker system with an extended phase lock range.

FIGS. 15A-C are flow diagrams of a method.

FIG. 16 is a graph of frequency versus OCT power spectrum.

FIG. 17 is a graph of frequency versus amplitude spectrum subtracted from the shot noise (experimental data) for the N=I (dotted line) and N=⅓ (solid line) cases.

FIG. 18 is a graph of power density for the full spectrum as a function of frequency.

FIG. 19 is a graph after subtraction of the shot noise levels.

FIG. 20 is a graph after processing the signals.

FIG. 21 is a graph of the coherence envelope for the coherently summed channels.

Background

The present invention describes a hybrid method that implements aspects of LCI and OCT where the reference arm is scanned, and spectral radar, which does not require reference arm scanning. The signal in the detection arm of an OCT system is split into more than one spectral band before detection. Each spectral band is detected by a separate photo detector and amplified. For each spectral band the signal is band pass filtered around the signal band by analog electronics and digitized, or, alternatively, the signal may be digitized and band pass filtered in software. As a consequence, the shot noise contribution to the signal is reduced by a factor equal to the number of spectral bands. The signal remains the same. The reduction of the shot noise increases the dynamic range and sensitivity of the system. In the limit of many detectors, no ranging or reference arm scanning is required and the method is similar to spectral radar except that phase information of the cross spectral density is preserved.

Theory

In current OCT system, the recombined light of sample and reference arm is detected by a single detector. The signal is determined by the interference of light reflected from sample and reference arm. For a single object in the sample arm, the OCT signal is proportional to the real part of the Fourier transform of the source spectrum S(k),
R(Δz)∝Re∫exp(ikΔz)S(k)dk,  (1)
with k=2π/λ=ω/c the free space wave number and Δz=z−z′ the path length difference between reference and sample waves respectively. R(z) is the interference part of the signal detected at the photo detectors. The intensity I(z) backscattered from the sample arm at location z is proportional to the square of the envelope of R(z),
I(z)∝R2(z).

Converting path length difference Δz to time difference τ between arrival of reference and sample waves, τ=Δz/c and using that the time difference τ is given by measurement time t times twice the speed of the reference mirror v divided by the speed of light c, τ=2vt/c, we obtain,
R(t)∝Re∫exp(iωtv/c)S(ω)dω,  (2)
with t the measurement time.

Fourier transforming the depth profile R(t), the frequency spectrum of the signal is obtained,
|R(ω)|∝|S(ωc/v)|,  (3)

This demonstrates that each angular frequency of the light source or equivalently each wavelength of the source is represented at its own frequency in the measured interferometric signal. The depth profile information R(t) can be obtained from the complex cross spectral density R(ω) by a Fourier transform.

The complex cross spectral density can also be obtained by splitting the signal R(t) in several spectral bands by means of a dispersive or interferometric element. At each detector, only part of the complex cross spectral density is determined. Combining the cross spectral densities of each detector, the full spectral density of the signal is retrieved.

Thus, the same information can be obtained by separating spectral components to individual detectors. Combining the signal of all detectors in software or hardware would result in the same signal as obtained with a single detector. However, a careful analysis of the noise present at each frequency in the case of many individual detectors, reveals that the shot noise contribution is significantly lower, leading to a significant signal to noise improvement. The signal to noise improvement is linearly dependent on the number of spectral bands in which the signal is split. Thus, two spectral bands give a signal to noise improvement of a factor of 2, four spectral bands give a signal to noise improvement of a factor of 4, etc.

Signal to Noise Analysis of Optical Coherence Tomography Signals in the Frequency Domain.

For a single reflector in the sample arm, the interference fringe signal as a function of position is given by
R(Δz)∝Re∫exp(ikΔz)S(k)dk,
or equivalently as a function of time,
R(t)∝Re∫exp(iωtv/c)S(ω)dω

The coherence envelope peak value is found by setting Δz=0 or t=0;
Ipeak∝∫S(k)dk∝∫S(ω)dω

In the frequency domain, the Fourier transform of R(t) is given by
R(ω)=∫R(t)eiωtdt=∫Re∫exp(iω′tv/c)S(ω′)dω′eiωtdt=Sc/v)

The peak value is given by
Ipeak∝∫R(ω)dω=∫Sc/2v)

In terms of electrical power, the signal is defined as Ipeak2. In the frequency domain, the signal is,
Ipeak2∝[∫R(ω)dω]2=[∫Sc/2v)dω]2 or in terms of sample and reference arm power,
Ipeak2∝[∫√{square root over (Srefc/2v))}*√{square root over (Ssamplec/2v))}dω]2=a(z)[∫Srefc/2v)dω]2,
with Ssample(ωc/2v)=a(z)Sref(ωc/2v) and a(z) the reflectivity at z.

Thus, the signal is proportional to a(z)[∫Sref(ωc/2v)dω]2.

The total power Pref is given by Pref=∫Sref(ωc/2v)dω

The shot noise has a white noise distribution and the shot noise density is proportional to the total power on the detector
Nshot(ω)∝∫Srefc/2v)dω=Pref

The shot noise density is given in units [W2/Hz], [A2/Hz] or [V2/Hz]. The total shot noise that contributes to the noise is the Shot noise density multiplied with the bandwidth BW, Nshot=Pref*BW

Using the above expressions for the Signal and Noise, the SNR ratio for a single detector is given by
SNR∝a(z)[∫Srefc/2v)dω]2/Pref*BW=Psample/BW.

For a two detector configuration, where the spectrum is equally split over two detectors, the bandwidth BW per detector is half, as is the reference power. For an individual detector in the two detector configuration the signal is given by an integration over half the signal bandwidth,

a ( z ) [ 0.5 * BW S ref ( ω c / 2 v ) ω ] 2 .
The noise is given by 0.5*Pref*0.5*BW and the SNR is now

S N R a ( z ) [ 0.5 BW S ref ( ω c / 2 v ) ω ] 2 / 0.5 P ref * 0.5 BW = P sample / BW .

The SNR is the same as in the previous case where the full spectrum was detected by a single detector.

To evaluate the Signal to noise for two detectors simultaneously, the signals of both detectors are coherently added after digital or analog band pass filtering, i.e., after Fourier transforming of the signal R(t) the frequency components R(ω) within the signal band of each detector are added to form the total signal in the frequency domain. The signal is,

I peak 2 a ( z ) [ 0.5 BW S ref ( ω c / 2 v ) ω + 0.5 BW S ref ( ω c / 2 v ) ω ] 2 = a ( z ) [ BW S ref ( ω c / 2 v ) ω ] 2 ,
which is equal to the signal if all the light was detected by a single detector.

The Noise is the sum of the noise at each detector. The individual detector noise was Nshot=0.5*Pref*0.5*BW. The sum of the noise of both detectors is Nshot=0.5*Pref*BW and the noise is half of what it was if the full spectrum or all the light was detected by a single detector. The SNR ratio in the case when each detector detects half the spectrum and the signal is coherently combined is,
SNR∝a(z)[∫Srefc/2v)dω]2/0.5*Pref*BW=2Psample/BW

Thus, the SNR is twice as high compared to if the full spectrum or all the light was detected by a single detector.

The gain in SNR is achieved because the shot noise has a white noise spectrum. An intensity present at the detector at frequency ω (or wavelength λ) contributes only to the signal at frequency ω, but the shot noise is generated at all frequencies. By narrowing the optical band width per detector, the shot noise contribution at each frequency is reduced, while the signal component remains the same.

Redundant SNR Arguments

The signal to noise can also be evaluated per frequency. The total SNR is given by,

S N R [ S N R ( ω ) ω ] 2 = a ( z ) P ref * BW [ S ref ( ω c / 2 v ) ω ] 2
which defines a SNR density as
√{square root over (SNR(ω))}∝Sref(ωc/2v)√{square root over (a(z))}/√{square root over (Pref*BW)},
which demonstrates that the SNR density at a particular frequency depends on the total pass band (BW) and the reference power of the signal at the particular detector.

For two detectors, where the spectrum is equally split over two detectors, the bandwidth BW is half, as is the reference power. For an individual detector in the two detector configuration the SNR density is given by,
√{square root over (SNR(ω))}∝Sref(ωc/2v)√{square root over (a(z))}/√{square root over (0.5Pref*0.5BW)}

From the above equation, it is clear that the SNR density increases as the spectral bandwidth at the detector is decreased.

One embodiment of the system of the present invention is shown in FIG. 1. The basic embodiment is an interferometer with a source arm, a sample arm, a reference arm, and a detection arm with a spectral demultiplexing unit, multiple detectors, optional analog processing electronics, and A/D conversion of all signals. The processing and display unit has optionally digital band pass filtering, Digital Fast Fourier Transforms (“FFT's”), coherent combination of signals, and data processing and display algorithms. The detector array may be 1×N for simple intensity ranging and imaging, 2×N for dual balanced detection, 2×N for polarization and/or Doppler sensitive detection, or 4×N for combined dual balanced and polarization and/or Doppler sensitive detection. Alternatively, an M×N array may be used for arbitrary M to allow detection of transverse spatial information on the sample.

Sources

The source arm contains a spatially coherent source that is used to illuminate the interferometer with low-coherence light. The source temporal coherence length is preferably shorter than a few microns (range is about 0.5 μm-30 μm). Examples of sources include, but are not limited to, semiconductor optical amplifier, superluminescent diodes, light-emitting diodes, solid-state femtosecond sources, amplified spontaneous emission, continuum sources, thermal sources, combinations thereof and the like.

Interferometer

The sample arm collects light reflected from the specimen and is combined with the light from the reference arm to form interference fringes. The reference arm reflects light back to be combined with the reference arm. This action of beam splitting/recombining may be performed using a beam splitter (Michelson), or circulator(s) (Mach-Zehnder) or other means known to those skilled in the art for separating a beam into multiple paths and recombining these multiple beams in a manner that interference between the beams may be detected. The splitting may be accomplished in free space or by using passive fiber optic or waveguide components.

Sample Arm

For LCI applications, the sample arm may be terminated by an optical probe comprising an cleaved (angled, flat, or polished) optical fiber or free space beam. A lens (aspherical, gradient index, spherical, diffractive, ball, drum) may be used to focus the beam on or within the sample. Beam directing elements may also be contained within the probe (mirror, prism, diffractive optical element) to direct the focused beam to a desired position on the sample for OCT applications, the position of the beam may be changed on the sample as a function of time, allowing reconstruction of a two-dimensional image. Altering the position of the focused beam on the sample may be accomplished by a scanning mirror (such as, but not limited to, a galvanometer or piezoelectric actuator), electrooptic actuator, moving the optical fiber (rotating the optical fiber, or linearly translating the optical fiber). The sample arm probe may be a fiber optic probe that has an internally moving element where the motion is initiated at a proximal end of the probe and the motion is conveyed by a motion transducing means (such as, but not limited to, wire, guidewire, speedometer cable, spring, optical fiber and the like) to the distal end. The fiber optic probe may be enclosed in a stationary sheath which is optically transparent where the light exits the probe at the distal end.

Reference Arm Delay

A delay mechanism in the reference arm allows for scanning the length or the group velocity of the reference arm. This delay is produced by stretching ah optical fiber, free space translational scanning using a piezoelectric transducer, or via a grating based pulse shaping optical delay line. As opposed to traditional LCI or OCT systems described in prior art, the reference arm in the present invention does not necessarily need to scan over the full ranging depth in the sample, but is required to scan over at least a fraction of the ranging depth equal to one over the number of detectors. This feature of the present invention is fundamentally different from delay scanning schemes used in LCI and OCT systems disclosed in prior art. The delay line optionally has a mechanism for generating a carrier frequency such as an acoustooptic modulator, electrooptic phase modulator or the like. In order to reduce the scan range of the reference arm, the spectrum needs to be split into spectral bands according to a method that will be explained below.

Detection

In the detection arm a spectral demultiplexing unit demultiplexes the spectral components to separate detectors. The detectors may consist of photodiodes (such as, but not limited to, silicon, InGaAs, extended InGaAs, and the like). Alternatively, a one or two dimensional array of detectors (such as, but not limited to, photodiode array, CCD, CMOS array, active CMOS array, CMOS “smart pixel” arrays, combinations thereof and the like) may be employed for detection. Two detectors for each spectral band may be used for polarization sensitive detection following separation of the recombined light into orthogonal polarization eigenstates. Detector arrays may be 1×N for simple intensity ranging and imaging, 2×N for dual balanced detection, 2×N for polarization and/or Doppler sensitive detection, or 4×N for combined dual balanced and polarization and/or Doppler sensitive detection. Alternatively, an M×N array may be used for arbitrary M to allow detection of transverse spatial information on the sample.

Detector signals are amplified by Trans Impedance Amplifiers (“TIA's”), band pass filtered (digitally or using analog circuitry) and digitized by A/D converters and stored in a computer for further processing. Each detector is preferably configured to be shot noise limited. Shot noise limited detection is achieved by adjusting the intensity of light returned from the reference arm so that the shot noise dominates over the thermal noise of the resistor in the TIA and is higher than the relative intensity noise (“RIN”). Each detector is balanced for such dual noise reduction.

In a broad aspect of the present invention, the number of detectors, N, can range from 2-10,000 or more. A preferred range of N is about 8-10,000 detectors. In one preferred embodiment, eight detectors (or a number in that area) can provide real time, or close to real time, imaging. When more than about one hundred detectors are used, it is likely that a custom array would need to be constructed.

Alternatively, another means for detection includes an integrating one-dimensional or two-dimensional CCD array which is capable of obtaining images at a rate greater than 1/f noise (approximately 10 kHz) (see FIG. 8). In this case the TIA is not needed and the BPF can be implemented discretely following digitization. An additional modification to this method includes using a second CCD for balanced detection which allows increased reference arm power and acquisition speed due to reduction of RIN. This method could be implemented using a single CCD with dual-balanced detection enabled by either interleaving dual balanced rows of the array detector or by placing two similar CCD detectors adjacent to one another.

Processing

The signal of each detector is band pass filtered around the signal frequency, such as by FFT's. The signal of all detectors can be combined as explained hereinabove to obtain the complex cross spectral density in the frequency domain. By Fourier transform, the complex cross spectral density can be converted to a depth profile in the tissue. Several methods to process the complex spectral density to obtain depth profile information are included by reference.

System Integration

Processing of the multiple signals may be performed using an imaging or diagnostic console which performs basic operations including, mathematical image reconstruction, display, data storage. Alternatively, another embodiment, shown in FIG. 2, envisions a standalone detection and processing system that may be connected to OCT and/or LCI systems already in use. In this case, the detector and digitization may be performed in the standalone unit. The input to the standalone unit would be the light combined from both reference and sample arms. The output of the system would be an interferometric signal similar to previous OCT or LCI console inputs, but with increased SNR. The standalone unit would contain the means for splitting the wavelengths into spectral bands, multiple detectors, analog electronics, including TIA's and means for reconstructing the interferometric signal. The means for reconstructing the interferometric signal would include either analog or digital means where the analog means includes band pass filters (“BPF's”), and analog means for adding the individual interferograms from each wavelength band. Digital means would include an analog to digital converter, CPU capable of recombining the interferograms from each spectral band into a single full bandwidth interferometric signal. The reconstructed interferogram may be then the output of the standalone system or alternatively, the reconstructed interferograms demodulated signal may be used as the input to the pre-existing system console.

Scan Range of the Reference Arm.

The ranging depth in the sample is determined by the resolution with which the cross spectral density can be determined. In a method using a single detector the spectral resolution of the complex spectral density is determined by the scan range of the reference arm. The larger the scan range, the higher the spectral resolution and the larger the ranging depth in the sample. In a system with a spectral demultiplexing unit and multiple detectors, the resolution of the cross spectral density is a combination of reference arm scan range and spectral demultiplexing characteristics.

Any suitable wavelength band shape may be used for demultiplexing. For arbitrary spectral band shapes, the scan range of the reference arm is determined by the maximum path length delay that is needed to completely resolve the spectral components in each band. In cases where the wavelength band is determined by successive non-overlapping optical bandpass filters, a full scan length is needed and the SNR improvement is achieved by decreasing the width of the BPF for each spectral bands.

For instance, in one preferred embodiment, as depicted in FIG. 3, the spectral demultiplexing unit can split the spectrum into two bands where each band consists of a set of narrow spectra in a comb-like structure. Interleaving the comb-like spectral bands of each detector gives back a continuous spectrum. The resolution needed to resolve the spectrum at an individual detector is half of what it would need to be in a single detector system, and thus the scan range of the reference arm can be reduced by a factor of two, while maintaining the same ranging depth in the sample. In an alternative embodiment, the spectral demultiplexing unit can be in the reference arm. In FIG. 4 an example is shown for splitting up the spectrum in four spectral bands. In this example the scan range of the reference arm can be reduced by a factor of four while maintaining the same ranging depth in the sample.

Embodiments of the Demultiplexing Filter

Several techniques are known to demultiplex or disperse the spectrum. One method would use a grating and a micro lens array to focus spectral components onto individual detectors. A second method would use prisms instead of a grating. A third method would use a grating and an addressable mirror array (such as, but not limited to, a “MEMS” mirror or digital light processing “DLP” apparatus or the like) to direct spectral components to individual detectors. A fourth method would use a linear array of optical filters prior to the array of individual detectors. A fifth method would use waveguides etched into a material or manufactured from fiber optic components to generate a pattern with the desired filter action. As an example, in FIG. 4 an embodiment of a wave guide filter is drawn that will split the spectrum into bands. A sixth method would use arrayed waveguide gratings (“AWG”) to create the interleaved or arbitrary spectral bands.

Relative Intensity Noise

One of the noise terms that are present at the detectors is relative intensity noise (“RIN”) or Bose-Einstein noise. For a system where the sample arm optical power is negligible compared to the reference arm optical power at the detectors, RIN will become dominant for spectral widths less than a few nanometers at trans impedance amplifier bandwidths of 1 MHz. For many detector configurations, the spectral width at each detector will be smaller than a few nanometers, and the relative intensity noise will dominate the overall system noise. Thus, balanced detection needs to be implemented to eliminate the RIN. Several methods known in the art exist to implement balanced detection. One method will be discussed in more detail. Light from the reference arm and sample arm is incident on a grating at slightly different angles and reflected and focused onto a linear N×M photo detector array. Along the N direction (column) of the array, wavelength is encoded. Along the M direction (row) of the array, the interference pattern of the sample and reference arm at a particular wavelength is recorded. Since sample and reference arm light were incident at slightly different angles, a pattern of interference maxima and minima will be present in the column direction. Balanced detection can be implemented by subtracting diode signals that are exactly out of phase with respect to the maxima and minima pattern. Alternatively, balanced detection can be implemented by measuring the amplitude of the interference pattern in the column direction which may be accomplished by subtracting the maxima or the interference pattern from the minima of the interference pattern along the column.

Signal Processing to Reconstruct the Signal after Spectral Demultiplexing and Detection.

Two cases will be discussed as nonlimiting illustrations of the present invention, firstly the case of continuous spectral bands (blocks), and secondly the comb-like spectral bands as depicted in FIGS. 2 and 3.

Case A: Continuous Spectral Bands.

The detection arm light is split into N spectral blocks, where each spectral block contains the intensity between two optical frequencies,

B N = ω N ω N + 1 S ref ( ω c / 2 v ) ω

The signal for the full spectral width is obtained by an FFT of the signal in each band, an optional compensation of dispersion and other corrections to the phase and amplitude of each Fourier component to optimize the signal and to correct the spectral density for side lobe reduction, addition of the complex FFT spectra, and inverse FFT on the added complex FFT spectrum, optionally with data reduction before the inverse FFT, to obtain the optionally demodulated function R(t), which is the interferometric response for a depth scan with the full source spectrum.

Case B: Comb Like Spectral Bands and the Reconstruction of the Full Depth Range in the Sample Arm from Reduced Reference Arm Scans.

The following discussion describes the principle of reconstruction of the full depth range in the sample arm from reduced reference arm scans. The procedure will be explained in the case of demultiplexing the spectrum in two spectral bands. The method can be expanded for demultiplexing into many spectral bands.

The signal at the detector for a single detector system is given by R(t). The depth range in the sample is given by the measurement time T of a single A-line (depth profile) times the group velocity generated by the reference arm delay line,
zrange=vgT

The smallest resolvable frequency after an FFT is given by 1/T, which gives a smallest resolvable angular frequency Δω=2π/T. The filter as depicted in FIG. 4 splits the signal into two bands with peaks at ω=ω0, ω0+2Δω, ω0+4Δω, etc. and ω=ω0+Δω, ω0+3Δω, etc., respectively.

B1(t) and B2 (t) are the signals in band one and two respectively. The signal in spectral bands one and two after Fourier transform are given by B1(ω)=R(ω)cos2(ωT/4) and B2(ω)=R(ω)sin2(ωT/4).

This product in the Fourier domain can also be written as a convolution in the time domain. Assuming the signals periodic with time T, the signals B1(t) and B2(t) are given by B1(t)=R(t)+R(t+T/2) and B2 (t)=R(t)−R(t+T/2).

Using the above equations, the signal R(t) from t=0 to t=T can be reconstructed from the signals B1(t) and B2 (t) recorded from t=0 to t=T/2 by writing, R(t)=B1(t)+B2 (t) and R(t+T/2=B1(t)−B2(t) for 0<t<T/2. For higher N>2, the identical procedure is performed such that R(t) is reconstructed from B1 to BN.

This demonstrates that the signals B1(t) and B2 (t) only need to be recorded over half the depth range zrange. Thus, the depth ranging in the reference arm can be reduced by a factor of 2 while the ranging depth in the sample remains the same. If the signal is split into more spectral bands, like shown in FIG. 3, a similar procedure as described above allows reduction of the depth scan in the reference arm by a factor of N, while the ranging depth in the sample remains the same, and N the number of spectral bands.

A flow diagram of the procedure described above is given in FIG. 7.

Case B2. Limit of Large Number of Spectral Bands

In the limit of a large number of spectral bands,

N L λ ,
the optical path length change in the reference arm approaches that of a wavelength, λ. In this limit, only a phase change across one wavelength is needed for reconstructing the entire axial scan over length L. In this case, the reference arm path delay may be accomplished by using any of the aforementioned means for scanning the reference arm delay. Other preferred methods include insertion of an electrooptic modulator, acoustooptic modulator or phase control rapidly scanning optical delay line (“RSOD”) in the reference arm path to impart the path length delay of one wavelength. Also in this case, the wavelength demultiplexing unit does not separate the wavelengths into a comb pattern, but demultiplexes the spectrum into unique optical frequencies, with each frequency detected by a single detector.
Case C. Fourier Domain Reconstruction for Arbitrary Wavelength Patterns

As opposed to reconstruction of the LCI or OCT signal in the time or space domains, the signal may be reconstructed in the Fourier domain by adding the complex spectral components for each wavelength band to compose the Fourier transform of the LCI or OCT signal. Alterations of the phase for each Fourier component may be needed in some circumstances to correct for minimization of reference arm delay length.

Reconstruction of the Image or One Dimensional Axial Scan

Following reconstruction of the LCI or OCT signal in the real domain, the axial reflectivity may be determined by demodulating the reconstructed LCI or OCT signal. Means for demodulation include, multiplication by a sinusoid and low pass filtering, envelope demodulation using envelope detection, square law demodulation and low pass filtering, quadrature demodulation followed by FIR, IIR filtering, or low pass filtering. In addition, known to those skilled in the art, is reconstruction of Stokes vectors (polarization) and flow from these LCI or OCT signals. Following reconstruction and demodulation, the data may be displayed in one or two-dimensional format (image) for interpretation and ultimately diagnosis of a tissue condition or defect in a medium. If one reconstructs the LCI or OCT signal in the Fourier domain, the reconstructed signal in the Fourier domain can be demodulated in the Fourier domain by shifting the Fourier spectrum and performing an inverse Fourier transform. As a result, the complex signal in the real domain (quadrature signal) is then reconstructed into axial reflectivity information by computing the amplitude of the real portion of the quadrature signal. The complex component is used for computing polarization or flow information. Alternatively, if the signal is reconstructed in the Fourier domain, it can be directly inverse Fourier transformed into the real domain and undergo the aforementioned processing described for the reconstructed real domain signals.

Advantages

The present invention reduces shot noise which allows for much lower source powers, or much higher acquisition rates than current systems. The increased detection sensitivity allows for real time imaging. Such imaging speed can help practitioners where motion artifacts are a continuing problem, such as in gastrointestinal, ophthalmic and arterial imaging environments. By increasing the frame rate while maintaining or improving the signal to noise ratio such artifacts can be minimized.

The invention will be further described in connection with the following examples, which are set forth for purposes of illustration only.

The method was verified in the lab by the following experiment.

In the existing OCT system, the shot noise power spectrum as determined from the spectral density due to the reference arm optical power was measured. Then ⅔ of the spectrum from the reference arm was blocked, and experimentally it was verified that the shot noise power spectrum was reduced by a factor of three, thus demonstrating that the shot noise is reduced by a factor of 3 if the spectrum is split in three spectral bands (see FIG. 5). The upper curve (gray dotted line) shows the power spectrum for the OCT signal with one detector. For the lower curve (solid line), the spectrum was limited by ⅓ with a corresponding factor of 3 improvement in signal to noise ratio. This data was generated by experiment, blocking ⅔ of the spectrum in a grating-based double-passed pulse shaping rapidly scanning optical delay line.

An object with low reflectivity was inserted in the sample arm. Using the full spectral width of the source, the power spectrum of the interference between sample and reference arm light was determined in the lower half of the spectral density. Then the upper part of the source spectrum was blocked in the reference arm, and it was verified that the lower ⅓ of the power spectrum of the interference between sample and reference arm light had the same magnitude as in the previous measurement (see FIG. 6). This figure demonstrates that the signal amplitude is equal for the N=1 and N=⅓ cases where they overlap. The result of equal amplitude signal for N=⅓ case and the 3-fold lower noise for the N=⅓ case (see FIG. 2) demonstrates that splitting into N wavelength bands increases the SNR by a factor of N.

This demonstrates that when the light in the detection arm is split in two spectral bands, the spectral density of the interference between sample and reference arm light within the spectral bandwidth of a single detector is unchanged. Combined with the measurement that showed a reduction in the shot noise power spectrum, the conclusion is that a reduction of shot noise can be realized by splitting the detection arm light in separate spectral bands.

Although only a few exemplary embodiments of this invention have been described in detail above, those skilled in the art will readily appreciate that many modifications are possible in the exemplary embodiments without materially departing from the novel teachings and advantages of this invention. Accordingly, all such modifications are intended to be included within the scope of this invention as defined in the following claims. It should further be noted that any patents, applications and publications referred to herein are incorporated by reference in their entirety.

Tearney, Guillermo J., Bouma, Brett Eugene, de Boer, Johannes F.

Patent Priority Assignee Title
10359271, Dec 05 2012 PERIMETER MEDICAL IMAGING, INC. System and method for tissue differentiation in imaging
10502544, Jun 15 2016 CARL ZEISS MEDITEC, INC Efficient sampling of optical coherence tomography data for explicit ranging over extended depth
10529061, Aug 13 2015 University of Washington Systems and methods of forming enhanced medical images
10577573, Jul 18 2017 PERIMETER MEDICAL IMAGING INC Sample container for stabilizing and aligning excised biological tissue samples for ex vivo analysis
10627613, Apr 10 2015 LLTECH MANAGEMENT Method and system for full-field interference microscopy imaging
10739245, Apr 26 2016 Cytek Biosciences, Inc.; CYTEK BIOSCIENCES, INC Compact multi-color flow cytometer
10894939, Jul 18 2017 PERIMETER MEDICAL IMAGING, INC. Sample container for stabilizing and aligning excised biological tissue samples for ex vivo analysis
11464408, Oct 03 2018 Notal Vision Ltd. Automatic optical path adjustment in home OCT
11543641, Apr 10 2015 LLTECH MANAGEMENT Method and system for full-field interference microscopy imaging
8610900, Mar 29 2010 NATIONAL TAIWAN UNIVERSITY Apparatus for low coherence optical imaging
8816284, Mar 30 2010 LAWRENCE LIVERMORE NATIONAL SECURITY, LLC LLNS Room-temperature quantum noise limited spectrometry and methods of the same
8901495, Mar 30 2010 Lawrence Livermore National Security, LLC.; LAWRENCE LIVERMORE NATIONAL SECURITY, LLC LLNS Room-temperature quantum noise limited spectrometry and methods of the same
9025150, May 18 2010 LLTECH MANAGEMENT Method and device for high resolution full field interference microscopy
9404801, Mar 30 2010 Lawrence Livermore National Security, LLC Room-temperature quantum noise limited spectrometry and methods of the same
9677869, Dec 05 2012 PERIMETER MEDICAL IMAGING, INC System and method for generating a wide-field OCT image of a portion of a sample
9970820, Mar 30 2010 Lawrence Livermore National Security, LLC Room-temperature quantum noise limited spectrometry and methods of the same
Patent Priority Assignee Title
2339754,
3090753,
3601480,
3856000,
3872407,
3941121, Dec 20 1974 The University of Cincinnati Focusing fiber-optic needle endoscope
3973219, Apr 24 1975 Research Corporation Very rapidly tuned cw dye laser
3983507, Jan 06 1975 Research Corporation Tunable laser systems and method
4030827, Dec 03 1973 Institut National de la Sante et de la Recherche Medicale (INSERM) Apparatus for the non-destructive examination of heterogeneous samples
4030831, Mar 22 1976 The United States of America as represented by the Secretary of the Navy Phase detector for optical figure sensing
4140364, Jun 23 1973 Olympus Optical Co., Ltd. Variable field optical system for endoscopes
4141362, May 23 1977 Richard Wolf GmbH Laser endoscope
4224929, Nov 08 1977 Olympus Optical Co., Ltd. Endoscope with expansible cuff member and operation section
4295738, Aug 30 1979 United Technologies Corporation Fiber optic strain sensor
4300816, Aug 30 1979 United Technologies Corporation Wide band multicore optical fiber
4303300, Feb 07 1979 Thomson-CSF Rotary-joint device providing for an optical waveguide transmission
4428643, Apr 08 1981 Xerox Corporation Optical scanning system with wavelength shift correction
4479499, Jan 29 1982 Method and apparatus for detecting the presence of caries in teeth using visible light
4533247, Sep 03 1981 STC plc Optical transmission system
4585349, Sep 12 1983 Battelle Memorial Institute Method of and apparatus for determining the position of a device relative to a reference
4601036, Sep 30 1982 Honeywell Inc. Rapidly tunable laser
4607622, Apr 11 1985 Charles D., Fritch Fiber optic ocular endoscope
4631498, Apr 26 1985 Agilent Technologies Inc CW Laser wavemeter/frequency locking technique
4639999, Nov 02 1984 Xerox Corporation High resolution, high efficiency I.R. LED printing array fabrication method
4650327, Oct 28 1985 HOSPIRA, INC Optical catheter calibrating assembly
4734578, Mar 27 1985 Olympus Optical Co., Ltd. Two-dimensional scanning photo-electric microscope
4744656, Dec 08 1986 BECTON DICKINSON CRITICAL CARE SYSTEMS PTE LTD Disposable calibration boot for optical-type cardiovascular catheter
4751706, Dec 31 1986 SAIC Laser for providing rapid sequence of different wavelengths
4763977, Jan 09 1985 HER MAJESTY IN RIGHT OF CANADA AS REPRESENTED BY THE MINISTER OF COMMUNICATIONS Optical fiber coupler with tunable coupling ratio and method of making
4770492, Oct 28 1986 Fitel USA Corporation Pressure or strain sensitive optical fiber
4827907, Nov 28 1986 Teac Optical Co., Ltd. Intra-observation apparatus
4834111, Jan 12 1987 TRUSTEES OF COLUMBIA UNIVERSITY, THE, A CORP OF NEW YORK Heterodyne interferometer
4868834, Sep 14 1988 UNITED STATES GOVERNMENT AS REPRESENTED BY THE SECRETAY OF THE ARMY System for rapidly tuning a low pressure pulsed laser
4890901, Dec 22 1987 Victor Company of Japan, Limited Color corrector for embedded prisms
4892406, Jan 11 1988 United Technologies Corporation; UNITED TECHNOLOGIES CORPORATION, A CORP OF DELAWARE Method of and arrangement for measuring vibrations
4905169, May 30 1986 Los Alamos National Security, LLC Method and apparatus for simultaneously measuring a plurality of spectral wavelengths present in electromagnetic radiation
4909631, Dec 18 1987 GENERAL SIGNAL CORPORATION, A CORP OF NY Method for film thickness and refractive index determination
4925302, Apr 13 1988 Agilent Technologies Inc Frequency locking device
4928005, Jan 25 1988 Thomson-CSF Multiple-point temperature sensor using optic fibers
4940328, Nov 04 1988 Georgia Tech Research Corporation Optical sensing apparatus and method
4965441, Jan 27 1988 Commissariat a l'Energie Atomique Method for the scanning confocal light-optical microscopic and indepth examination of an extended field and devices for implementing said method
4965599, Nov 13 1989 Eastman Kodak Company Scanning apparatus for halftone image screen writing
4966589, Nov 14 1988 FLUIDICS INTERNATIONAL, INC Intravenous catheter placement device
4984888, Dec 13 1989 IMO INDUSTRIES, INC Two-dimensional spectrometer
4993834, Oct 03 1988 Fried. Krupp GmbH Spectrometer for the simultaneous measurement of intensity in various spectral regions
4998972, Apr 28 1988 Thomas J., Fogarty Real time angioscopy imaging system
5039193, Apr 03 1990 Focal Technologies Corporation Fibre optic single mode rotary joint
5040889, May 30 1986 BYK -GARDNER USA, DIVISION OF ALTANA INC , Spectrometer with combined visible and ultraviolet sample illumination
5045936, Jul 25 1988 KEYMED MEDICAL & INDUSTRIAL EQUIPMENT LIMITED Laser scanning imaging apparatus and method of ranging
5046501, Jan 18 1989 Wayne State University Atherosclerotic identification
5065331, May 19 1985 General Electric Company Apparatus and method for determining the stress and strain in pipes, pressure vessels, structural members and other deformable bodies
5085496, Mar 31 1989 SHARP KABUSHIKI KAIHSA, Optical element and optical pickup device comprising it
5120953, Jul 13 1988 OPTISCAN PTY LIMITED Scanning confocal microscope including a single fibre for transmitting light to and receiving light from an object
5121983, Dec 14 1989 Goldstar Co., Ltd. Stereoscopic projector
5127730, Aug 10 1990 REGENTS OF THE UNIVERSITY OF MINNESOTA, A NON-PROFIT CORP OF MN Multi-color laser scanning confocal imaging system
5197470, Jul 16 1990 CLINICAL DIAGNOSTIC SYSTEMS INC Near infrared diagnostic method and instrument
5202745, Nov 07 1990 Agilent Technologies Inc Polarization independent optical coherence-domain reflectometry
5202931, Oct 06 1987 Cell Analysis Systems, Inc. Methods and apparatus for the quantitation of nuclear protein
5208651, Jul 16 1991 Regents of the University of California, The Apparatus and method for measuring fluorescence intensities at a plurality of wavelengths and lifetimes
5212667, Feb 03 1992 General Electric Company Light imaging in a scattering medium, using ultrasonic probing and speckle image differencing
5214538, Jul 25 1988 Keymed (Medical and Industrial Equipment) Limited Optical apparatus
5217456, Feb 24 1992 PDT Cardiovascular, Inc. Device and method for intra-vascular optical radial imaging
5228001, Jan 23 1991 Syracuse University Optical random access memory
5241364, Oct 19 1990 Fuji Photo Film Co., Ltd. Confocal scanning type of phase contrast microscope and scanning microscope
5248876, Apr 21 1992 International Business Machines Corporation Tandem linear scanning confocal imaging system with focal volumes at different heights
5250186, Oct 23 1990 Cetus Corporation HPLC light scattering detector for biopolymers
5251009, Jan 22 1990 Ciba-Geigy Corporation Interferometric measuring arrangement for refractive index measurements in capillary tubes
5262644, Jun 29 1990 Southwest Research Institute Remote spectroscopy for raman and brillouin scattering
5275594, Nov 09 1990 RARE EARTH MEDICAL, INC Angioplasty system having means for identification of atherosclerotic plaque
5281811, Jun 17 1991 MOOG COMPONENTS GROUP INC Digital wavelength division multiplex optical transducer having an improved decoder
5283795, Apr 21 1992 HE HOLDINGS, INC , A DELAWARE CORP ; Raytheon Company Diffraction grating driven linear frequency chirped laser
5291885, Nov 27 1990 Kowa Company Ltd. Apparatus for measuring blood flow
5293872, Apr 03 1991 MEDISCIENCE TECHNOLOGY CORP , A CORP OF NEW JERSEY Method for distinguishing between calcified atherosclerotic tissue and fibrous atherosclerotic tissue or normal cardiovascular tissue using Raman spectroscopy
5293873, Aug 29 1991 Siemens Aktiengesellschaft Measuring arrangement for tissue-optical examination of a subject with visible, NIR or IR light
5302025, Aug 06 1982 Optical systems for sensing temperature and other physical parameters
5304173, Mar 22 1985 Massachusetts Institute of Technology Spectral diagonostic and treatment system
5304810, Jul 18 1990 Medical Research Council Confocal scanning optical microscope
5305759, Sep 26 1990 Olympus Optical Co., Ltd. Examined body interior information observing apparatus by using photo-pulses controlling gains for depths
5317389, Jun 12 1989 California Institute of Technology Method and apparatus for white-light dispersed-fringe interferometric measurement of corneal topography
5318024, Mar 22 1985 Massachusetts Institute of Technology Laser endoscope for spectroscopic imaging
5321501, Apr 29 1991 Massachusetts Institute of Technology Method and apparatus for optical imaging with means for controlling the longitudinal range of the sample
5348003, Sep 03 1992 Nellcor Puritan Bennett Incorporated Method and apparatus for chemical analysis
5353790, Jan 17 1992 Board of Regents, The University of Texas System Method and apparatus for optical measurement of bilirubin in tissue
5383467, Nov 18 1992 SPECTRASCIENCE, INC A K A GV MEDICAL, INC Guidewire catheter and apparatus for diagnostic imaging
5394235, Mar 17 1993 Ando Electric Co., Ltd.; Nippon Telegraph and Telephone Corporation Apparatus for measuring distortion position of optical fiber
5404415, Jan 27 1993 Shin-Etsu Chemical Co., Ltd. Optical fiber coupler and method for preparing same
5411016, Feb 22 1994 Boston Scientific Scimed, Inc Intravascular balloon catheter for use in combination with an angioscope
5419323, Nov 17 1989 Massachusetts Institute of Technology Method for laser induced fluorescence of tissue
5424827, Apr 30 1993 B F GOODRICH COMPANY, THE Optical system and method for eliminating overlap of diffraction spectra
5439000, Nov 18 1992 SPECTRASCIENCE, INC Method of diagnosing tissue with guidewire
5441053, May 03 1991 UNIV OF KY RESEARCH FOUNDATION Apparatus and method for multiple wavelength of tissue
5450203, Dec 22 1993 MARTEK, INC Method and apparatus for determining an objects position, topography and for imaging
5454807, May 14 1993 Boston Scientific Scimed, Inc Medical treatment of deeply seated tissue using optical radiation
5459325, Jul 19 1994 GE Healthcare Bio-Sciences Corp High-speed fluorescence scanner
5459570, Apr 29 1991 Massachusetts Institute of Technology Method and apparatus for performing optical measurements
5465147, Apr 29 1991 Massachusetts Institute of Technology Method and apparatus for acquiring images using a ccd detector array and no transverse scanner
5486701, Jun 16 1992 Prometrix Corporation Method and apparatus for measuring reflectance in two wavelength bands to enable determination of thin film thickness
5491524, Oct 05 1994 Carl Zeiss, Inc. Optical coherence tomography corneal mapping apparatus
5491552, Mar 29 1993 Bruker Medizintechnik Optical interferometer employing mutually coherent light source and an array detector for imaging in strongly scattered media
5522004, Apr 30 1993 Telefonaktiebolaget LM Ericsson Device and method for dispersion compensation in a fiber optic transmission system
5526338, Mar 10 1995 Yeda Research & Development Co. Ltd. Method and apparatus for storage and retrieval with multilayer optical disks
5555087, Jun 15 1993 TOPCON CORPORATION Method and apparatus for employing a light source and heterodyne interferometer for obtaining information representing the microstructure of a medium at various depths therein
5562100, Dec 21 1988 Massachusetts Institute of Technology Method for laser induced fluorescence of tissue
5565983, May 26 1995 Perkin Elmer LLC Optical spectrometer for detecting spectra in separate ranges
5565986, Mar 30 1994 ISIS Sentronics GmbH Stationary optical spectroscopic imaging in turbid objects by special light focusing and signal detection of light with various optical wavelengths
5566267, Dec 15 1994 CERAMOPTEC INDUSTRIES, INC Flat surfaced optical fibers and diode laser medical delivery devices
5583342, Jun 03 1993 Hamamatsu Photonics K.K. Laser scanning optical system and laser scanning optical apparatus
5590660, Mar 28 1994 NOVADAQ TECHNOLOGIES INC Apparatus and method for imaging diseased tissue using integrated autofluorescence
5600486, Jan 30 1995 Lockheed Corporation; Lockheed Martin Corporation Color separation microlens
5601087, Nov 18 1992 SpectraScience, Inc. System for diagnosing tissue with guidewire
5621830, Jun 07 1995 Smith & Nephew, Inc Rotatable fiber optic joint
5623336, Apr 30 1993 Method and apparatus for analyzing optical fibers by inducing Brillouin spectroscopy
5635830, Mar 29 1993 Matsushita Electric Industrial Co., Ltd. Optical magnetic field sensor employing differently sized transmission lines
5649924, Jun 10 1988 CATHETER ABLATION SOLUTIONS LLC Medical device for irradiation of tissue
5697373, Mar 14 1995 Board of Regents, The University of Texas System Optical method and apparatus for the diagnosis of cervical precancers using raman and fluorescence spectroscopies
5698397, Jun 07 1995 SRI International Up-converting reporters for biological and other assays using laser excitation techniques
5710630, May 05 1994 Boehringer Mannheim GmbH Method and apparatus for determining glucose concentration in a biological sample
5716324, Aug 25 1992 FUJIFILM Corporation Endoscope with surface and deep portion imaging systems
5719399, Dec 18 1995 RESEARCH FOUNDATION OF CITY COLLEGE OF NEW YORK, THE Imaging and characterization of tissue based upon the preservation of polarized light transmitted therethrough
5730731, Apr 28 1988 Thomas J., Fogarty Pressure-based irrigation accumulator
5735276, Mar 21 1995 Method and apparatus for scanning and evaluating matter
5740808, Oct 28 1996 EP Technologies, Inc Systems and methods for guilding diagnostic or therapeutic devices in interior tissue regions
5748318, Aug 06 1996 Brown University Research Foundation Optical stress generator and detector
5748598, Dec 22 1995 Massachusetts Institute of Technology Apparatus and methods for reading multilayer storage media using short coherence length sources
5752518, Oct 28 1996 EP Technologies, Inc. Systems and methods for visualizing interior regions of the body
5784352, Jul 21 1995 Massachusetts Institute of Technology Apparatus and method for accessing data on multilayered optical media
5785651, Jun 07 1995 ADDITION TECHNOLOGY, INC Distance measuring confocal microscope
5795295, Jun 25 1996 Carl Zeiss, Inc. OCT-assisted surgical microscope with multi-coordinate manipulator
5801826, Feb 18 1997 WILLIAMS FAMILY TRUST B, RICHARD K WILLIAMS, TRUSTEE Spectrometric device and method for recognizing atomic and molecular signatures
5801831, Sep 20 1996 CENTRE FOR RESEARCH IN EARTH AND SPACE TECHNOLOGY CRESTECH Fabry-Perot spectrometer for detecting a spatially varying spectral signature of an extended source
5803082, Nov 09 1993 Staplevision Inc. Omnispectramammography
5807261, Feb 26 1993 JB IP ACQUISITION LLC Noninvasive system for characterizing tissue in vivo
5810719, Aug 25 1992 Fuji Photo Film Co., Ltd. Endoscope
5817144, Oct 25 1994 THE SPECTRANETICS CORPORATION Method for contemporaneous application OF laser energy and localized pharmacologic therapy
5836877, Feb 24 1997 CALIBER IMAGING & DIAGNOSTICS, INC System for facilitating pathological examination of a lesion in tissue
5840023, Jan 31 1996 SENO MEDICAL INSTRUMENTS, INC Optoacoustic imaging for medical diagnosis
5840075, Aug 23 1996 Eclipse Surgical Technologies, Inc. Dual laser device for transmyocardial revascularization procedures
5842995, Jun 28 1996 Board of Regents, The University of Texas System Spectroscopic probe for in vivo measurement of raman signals
5843000, May 07 1996 The General Hospital Corporation Optical biopsy forceps and method of diagnosing tissue
5843052, Oct 04 1996 Irrigation kit for application of fluids and chemicals for cleansing and sterilizing wounds
5847827, Jun 23 1995 Carl Zeiss Jena GmbH Coherence biometry and coherence tomography with dynamic coherent
5862273, Feb 21 1997 KAISER OPTICAL SYSTEMS, INC Fiber optic probe with integral optical filtering
5865754, Aug 23 1996 Texas A&M University System Fluorescence imaging system and method
5867268, Mar 01 1995 Imalux Corporation Optical fiber interferometer with PZT scanning of interferometer arm optical length
5871449, Dec 27 1996 Volcano Corporation Device and method for locating inflamed plaque in an artery
5872879, Nov 25 1996 Boston Scientific Corporation Rotatable connecting optical fibers
5877856, May 14 1996 Carl Zeiss Jena GmbH Methods and arrangement for increasing contrast in optical coherence tomography by means of scanning an object with a dual beam
5887009, May 22 1997 OPTICAL BIOPSY TECHNOLOGIES, INC Confocal optical scanning system employing a fiber laser
5892583, Aug 21 1997 High speed inspection of a sample using superbroad radiation coherent interferometer
5910839, Feb 05 1996 Lawrence Livermore National Security LLC White light velocity interferometer
5912764, Sep 18 1996 Olympus Optical Co., Ltd. Endoscope optical system and image pickup apparatus
5920373, Sep 24 1997 Heidelberg Engineering Optische Messysteme GmbH Method and apparatus for determining optical characteristics of a cornea
5920390, Jun 26 1997 University of North Carolina; Charlotte-Mecklenburg Hospital Authority Fiberoptic interferometer and associated method for analyzing tissue
5921926, Jul 28 1997 Research Foundation of the University of Central Florida, Inc Three dimensional optical imaging colposcopy
5926592, Mar 24 1995 Optiscan PTY LTD Optical fibre confocal imager with variable near-confocal control
5949929, Nov 25 1996 Boston Scientific Corporation Rotatably connecting optical fibers
5951482, Oct 03 1997 THE SPECTRANETICS CORPORATION Assemblies and methods for advancing a guide wire through body tissue
5955737, Oct 27 1997 Systems & Processes Engineering Corporation Chemometric analysis for extraction of individual fluorescence spectrum and lifetimes from a target mixture
5956355, Apr 29 1991 Massachusetts Institute of Technology Method and apparatus for performing optical measurements using a rapidly frequency-tuned laser
5968064, Feb 28 1997 CARDINAL HEALTH SWITZERLAND 515 GMBH Catheter system for treating a vascular occlusion
5975697, Nov 25 1998 OPTOS PLC Optical mapping apparatus with adjustable depth resolution
5983125, Dec 13 1993 The Research Foundation of City College of New York Method and apparatus for in vivo examination of subcutaneous tissues inside an organ of a body using optical spectroscopy
5987346, Feb 26 1993 JB IP ACQUISITION LLC Device and method for classification of tissue
5991697, Dec 31 1996 CALIFORNIA, UNIVERSITY OF, REGENTS OF THE, THE Method and apparatus for optical Doppler tomographic imaging of fluid flow velocity in highly scattering media
5994690, Mar 17 1997 Image enhancement in optical coherence tomography using deconvolution
5995223, Jun 01 1998 Apparatus for rapid phase imaging interferometry and method therefor
6002480, Jun 02 1997 Depth-resolved spectroscopic optical coherence tomography
6004314, Aug 18 1994 Carl Zeiss, Inc. Optical coherence tomography assisted surgical apparatus
6006128, Jun 02 1997 Doppler flow imaging using optical coherence tomography
6007996, Dec 12 1995 Applied Spectral Imaging Ltd. In situ method of analyzing cells
6010449, Feb 28 1997 CARDINAL HEALTH SWITZERLAND 515 GMBH Intravascular catheter system for treating a vascular occlusion
6014214, Aug 21 1997 High speed inspection of a sample using coherence processing of scattered superbroad radiation
6016197, Aug 25 1995 CeramOptec Industries Inc. Compact, all-optical spectrum analyzer for chemical and biological fiber optic sensors
6020963, Jun 04 1996 Northeastern University Optical quadrature Interferometer
6025956, Dec 26 1995 Olympus Optical Co., Ltd. Incident-light fluorescence microscope
6033721, Oct 26 1994 Fei Company Image-based three-axis positioner for laser direct write microchemical reaction
6037579, Nov 13 1997 Biophotonics Information Laboratories, Ltd. Optical interferometer employing multiple detectors to detect spatially distorted wavefront in imaging of scattering media
6044288, Nov 08 1996 Imaging Diagnostics Systems, Inc. Apparatus and method for determining the perimeter of the surface of an object being scanned
6045511, Apr 21 1997 Dipl-Ing. Lutz Ott Device and evaluation procedure for the depth-selective, noninvasive detection of the blood flow and/or intra and/or extra-corporeally flowing liquids in biological tissue
6048742, Feb 26 1998 The United States of America as represented by the Secretary of the Air Process for measuring the thickness and composition of thin semiconductor films deposited on semiconductor wafers
6053613, May 15 1998 Carl Zeiss, Inc. Optical coherence tomography with new interferometer
6069698, Aug 28 1997 Olympus Corporation Optical imaging apparatus which radiates a low coherence light beam onto a test object, receives optical information from light scattered by the object, and constructs therefrom a cross-sectional image of the object
6078047, Mar 14 1997 THE CHASE MANHATTAN BANK, AS COLLATERAL AGENT Method and apparatus for terahertz tomographic imaging
6091496, Jan 28 1997 Zetetic Institute Multiple layer, multiple track optical disk access by confocal interference microscopy using wavenumber domain reflectometry and background amplitude reduction and compensation
6091984, Oct 10 1997 Massachusetts Institute of Technology Measuring tissue morphology
6094274, Jun 05 1998 Olympus Corporation Fluorescence detecting device
6107048, Nov 20 1997 MEDICAL COLLEGE OF GEORGIA RESEARCH INSTITUTE, INC , A CORPORATION OF GEORGIA Method of detecting and grading dysplasia in epithelial tissue
6111645, Apr 29 1991 Massachusetts Institute of Technology Grating based phase control optical delay line
6117128, Apr 30 1997 Providence Health System - Oregon Energy delivery catheter and method for the use thereof
6120516, Feb 28 1997 CARDINAL HEALTH SWITZERLAND 515 GMBH Method for treating vascular occlusion
6134003, Apr 29 1991 General Hospital Corporation, The Method and apparatus for performing optical measurements using a fiber optic imaging guidewire, catheter or endoscope
6134010, Nov 07 1997 CALIBER IMAGING & DIAGNOSTICS, INC Imaging system using polarization effects to enhance image quality
6134033, Feb 26 1998 TYCO TELECOMMUNICATIONS US INC Method and apparatus for improving spectral efficiency in wavelength division multiplexed transmission systems
6141577, Jul 28 1997 Research Foundation of the University of Central Florida, Inc Three dimensional optical imaging colposcopy
6151522, Mar 16 1998 Avery Dennison Corporation; RESEARCH FOUNDATION OF CUNY, THE Method and system for examining biological materials using low power CW excitation raman spectroscopy
6159445, Dec 04 1997 GE HEALTHCARE AS Light imaging contrast agents
6160826, Apr 29 1991 Massachusetts Institute of Technology Method and apparatus for performing optical frequency domain reflectometry
6161031, Aug 10 1990 Board of Regents of the University of Washington Optical imaging methods
6166373, Jul 21 1998 The Institute for Technology Development Focal plane scanner with reciprocating spatial window
6174291, Mar 09 1998 SpectraScience, Inc. Optical biopsy system and methods for tissue diagnosis
6175669, Mar 30 1998 Lawrence Livermore National Security LLC Optical coherence domain reflectometry guidewire
6185271, Feb 16 1999 Helical computed tomography with feedback scan control
6191862, Jan 20 1999 LIGHTLAB IMAGING, INC Methods and apparatus for high speed longitudinal scanning in imaging systems
6193676, Oct 03 1997 THE SPECTRANETICS CORPORATION Guide wire assembly
6198956, Sep 30 1999 OPTOS PLC High speed sector scanning apparatus having digital electronic control
6201989, Mar 13 1997 BIOMAX TECHNOLOGIES, INC Methods and apparatus for detecting the rejection of transplanted tissue
6208415, Jun 12 1997 Regents of the University of California, The Birefringence imaging in biological tissue using polarization sensitive optical coherent tomography
6208887, Jun 24 1999 PRESCIENT MEDICAL, INC Catheter-delivered low resolution Raman scattering analyzing system for detecting lesions
6245026, Jul 29 1996 VOLCANO THERAPEUTICS, INC Thermography catheter
6249349, Sep 27 1996 Microscope generating a three-dimensional representation of an object
6249381, May 13 1998 Sony Corporation Illuminating method and illuminating device
6249630, Dec 13 1996 Imra America Apparatus and method for delivery of dispersion-compensated ultrashort optical pulses with high peak power
6263234, Oct 01 1996 Leica Microsystems CMS GmbH Confocal surface-measuring device
6264610, May 05 1999 CONNECTICUT, UNIVERSITY OF, THE Combined ultrasound and near infrared diffused light imaging system
6272376, Jan 22 1999 SOUTHERN CALIFORNIA, UNIVERSITY OF Time-resolved, laser-induced fluorescence for the characterization of organic material
6274871, Oct 22 1998 VYSIS, INC Method and system for performing infrared study on a biological sample
6282011, Apr 29 1991 Massachusetts Institute of Technology Grating based phase control optical delay line
6297018, Sep 24 1998 MDS ANALYTICAL TECHNOLOGIES US INC Methods and apparatus for detecting nucleic acid polymorphisms
6301048, May 19 2000 Avanex Corporation Tunable chromatic dispersion and dispersion slope compensator utilizing a virtually imaged phased array
6308092, Oct 13 1999 C. R. Bard Inc. Optical fiber tissue localization device
6324419, Oct 27 1998 MEDICINE AND DENTISTRY OF NEW JERSEY, UNIVERSITY OF; NEW JERSEY INSTITUTE OF TECHNOLOGY UNIVERSITY HEIGHTS Apparatus and method for non-invasive measurement of stretch
6341036, Feb 26 1998 The General Hospital Corporation Confocal microscopy with multi-spectral encoding
6353693, May 31 1999 Yamaha Hatsudoki Kabushiki Kaisha Optical communication device and slip ring unit for an electronic component-mounting apparatus
6359692, Jul 09 1999 Zygo Corporation Method and system for profiling objects having multiple reflective surfaces using wavelength-tuning phase-shifting interferometry
6374128, Nov 20 1998 FUJIFILM Corporation Blood vessel imaging system
6377349, Mar 30 1998 Carl Zeiss Jena GmbH Arrangement for spectral interferometric optical tomography and surface profile measurement
6384915, Mar 30 1998 Lawrence Livermore National Security LLC Catheter guided by optical coherence domain reflectometry
6393312, Oct 13 1999 C. R. Bard, Inc. Connector for coupling an optical fiber tissue localization device to a light source
6394964, Mar 09 1998 SPECTRASCIENCE, INC Optical forceps system and method of diagnosing and treating tissue
6396941, Aug 23 1996 EVIDENT SCIENTIFIC, INC Method and apparatus for internet, intranet, and local viewing of virtual microscope slides
6421164, Apr 29 1991 Massachusetts Institute of Technology Interferometeric imaging with a grating based phase control optical delay line
6437867, Dec 04 1996 RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK, THE Performing selected optical measurements with optical coherence domain reflectometry
6441892, Nov 19 1999 HORIBA INSTRUMENTS INCORPORATED Compact spectrofluorometer
6441959, May 19 2000 II-VI Incorporated; MARLOW INDUSTRIES, INC ; EPIWORKS, INC ; LIGHTSMYTH TECHNOLOGIES, INC ; KAILIGHT PHOTONICS, INC ; COADNA PHOTONICS, INC ; Optium Corporation; Finisar Corporation; II-VI OPTICAL SYSTEMS, INC ; M CUBED TECHNOLOGIES, INC ; II-VI PHOTONICS US , INC ; II-VI DELAWARE, INC; II-VI OPTOELECTRONIC DEVICES, INC ; PHOTOP TECHNOLOGIES, INC Method and system for testing a tunable chromatic dispersion, dispersion slope, and polarization mode dispersion compensator utilizing a virtually imaged phased array
6445485, Jan 21 2000 AT&T Corp. Micro-machine polarization-state controller
6445939, Aug 09 1999 LIGHTLAB IMAGING, INC Ultra-small optical probes, imaging optics, and methods for using same
6445944, Feb 01 1999 Boston Scientific Scimed, Inc Medical scanning system and related method of scanning
6459487, Sep 05 2000 ARROYO OPTICS, INC System and method for fabricating components of precise optical path length
6463313, Jul 09 1997 THE SPECTRANETICS CORPORATION Systems for guiding a medical instrument through a body
6469846, Jun 29 2000 Riken Grism
6475159, Sep 20 1995 Board of Regents, University of Texas System Method of detecting vulnerable atherosclerotic plaque
6475210, Feb 11 2000 PHELPS, DAVID Y Light treatment of vulnerable atherosclerosis plaque
6477403, Aug 09 1999 Asahi Kogaku Kogyo Kabushiki Kaisha Endoscope system
6485413, Apr 29 1991 General Hospital Corporation, The Methods and apparatus for forward-directed optical scanning instruments
6485482, Jul 30 1999 Boston Scientific Scimed, Inc Rotational and translational drive coupling for catheter assembly
6501551, Apr 29 1991 Massachusetts Institute of Technology Fiber optic imaging endoscope interferometer with at least one faraday rotator
6501878, Dec 14 2000 Lumentum Technology UK Limited Optical fiber termination
6516014, Nov 13 1998 Montana State University Programmable frequency reference for laser frequency stabilization, and arbitrary optical clock generator, using persistent spectral hole burning
6517532, May 15 1997 PALOMAR MEDICAL TECHNOLOGIES, LLC Light energy delivery head
6538817, Oct 25 1999 Lockheed Martin Corporation Method and apparatus for optical coherence tomography with a multispectral laser source
6540391, Apr 27 2000 IRIDEX Corporation Method and apparatus for real-time detection, control and recording of sub-clinical therapeutic laser lesions during ocular laser photocoagulation
6549801, Jun 11 1998 Regents of the University of California, The Phase-resolved optical coherence tomography and optical doppler tomography for imaging fluid flow in tissue with fast scanning speed and high velocity sensitivity
6552796, Apr 06 2001 LIGHTLAB IMAGING, INC Apparatus and method for selective data collection and signal to noise ratio enhancement using optical coherence tomography
6556305, Feb 17 2000 Bruker Nano Inc Pulsed source scanning interferometer
6556853, Dec 12 1995 Applied Spectral Imaging Ltd. Spectral bio-imaging of the eye
6558324, Nov 22 2000 Siemens Medical Solutions, Inc., USA System and method for strain image display
6564087, Apr 29 1991 Massachusetts Institute of Technology Fiber optic needle probes for optical coherence tomography imaging
6564089, Feb 04 1999 Olympus Corporation Optical imaging device
6567585, Apr 04 2000 Optiscan PTY LTD Z sharpening for fibre confocal microscopes
6593101, Mar 28 2000 Board of Regents, The University of Texas System Enhancing contrast in biological imaging
6611833, Jun 23 1999 Ventana Medical Systems, Inc Methods for profiling and classifying tissue using a database that includes indices representative of a tissue population
6615071, Sep 20 1995 Board of Regents, The University of Texas System Method and apparatus for detecting vulnerable atherosclerotic plaque
6622732, Jul 15 1998 CARDINAL HEALTH SWITZERLAND 515 GMBH Methods and devices for reducing the mineral content of vascular calcified lesions
6654127, Mar 01 2001 CARL ZEISS MEDITEC, INC Optical delay line
6657730, Jan 04 2001 Interferometer with angled beam entry
6658278, Oct 17 2001 TERUMO CORPORATION OF JAPAN Steerable infrared imaging catheter having steering fins
6680780, Dec 23 1999 Bell Semiconductor, LLC Interferometric probe stabilization relative to subject movement
6685885, Jun 22 2001 Purdue Research Foundation Bio-optical compact dist system
6687007, Dec 14 2000 Kestrel Corporation Common path interferometer for spectral image generation
6687010, Sep 09 1999 Olympus Corporation Rapid depth scanning optical imaging device
6687036, Nov 03 2000 NUONICS, INC Multiplexed optical scanner technology
6692430, Apr 10 2000 GYRUS ACMI, INC D B A OLYMPUS SURGICAL TECHNOLOGIES AMERICA Intra vascular imaging apparatus
6701181, May 31 2001 INFRAREDX, INC Multi-path optical catheter
6721094, Mar 05 2001 National Technology & Engineering Solutions of Sandia, LLC Long working distance interference microscope
6738144, Dec 17 1999 University of Central Florida Non-invasive method and low-coherence apparatus system analysis and process control
6741355, Nov 20 2000 TAYLOR HOBSON LTD Short coherence fiber probe interferometric measuring device
6757467, Jul 25 2000 Optical Air Data Systems, LLC Optical fiber system
6790175, Oct 28 1999 PENTAX Corporation Endoscope system
6806963, Nov 24 1999 Haag-Streit AG Method and device for measuring the optical properties of at least two regions located at a distance from one another in a transparent and/or diffuse object
6816743, Oct 08 1998 University of Kentucky Research Foundation Methods and apparatus for in vivo identification and characterization of vulnerable atherosclerotic plaques
6831781, Feb 26 1998 General Hospital Corporation, The Confocal microscopy with multi-spectral encoding and system and apparatus for spectroscopically encoded confocal microscopy
6839496, Jun 28 1999 LONDON, UNIVERISTY COLLEGE Optical fibre probe for photoacoustic material analysis
6882432, Aug 08 2000 Zygo Corporation Frequency transform phase shifting interferometry
6900899, Aug 20 2001 Keysight Technologies, Inc Interferometers with coated polarizing beam splitters that are rotated to optimize extinction ratios
6903820, Jun 04 2003 SAMSUNG ELECTRONICS CO , LTD Measurements of substances using two different propagation modes of light through a common optical path
6909105, Mar 02 1999 MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN E V Method and device for representing an object
6949072, Sep 22 2003 INFRAREDX, INC Devices for vulnerable plaque detection
6961123, Sep 28 2001 TEXAS A&M UNIVERSITY SYSTEM, THE Method and apparatus for obtaining information from polarization-sensitive optical coherence tomography
6980299, Oct 16 2001 General Hospital Corporation Systems and methods for imaging a sample
6996549, May 01 1998 Health Discovery Corporation Computer-aided image analysis
7006231, Oct 18 2001 Boston Scientific Scimed, Inc Diffraction grating based interferometric systems and methods
7006232, Apr 05 2002 Case Western Reserve University; University of Hospitals of Cleveland Phase-referenced doppler optical coherence tomography
7019838, May 30 2003 Duke University System and method for low coherence broadband quadrature interferometry
7027633, Nov 30 2000 Rutgers, The State University of New Jersey Collaborative diagnostic systems
7061622, Aug 03 2001 University Hospitals of Cleveland; Case Western Reserve University Aspects of basic OCT engine technologies for high speed optical coherence tomography and light source and other improvements in optical coherence tomography
7072047, Jul 12 2002 University Hospitals of Cleveland; Case Western Reserve University Method and system for quantitative image correction for optical coherence tomography
7075658, Jan 24 2003 Duke University; Case Western Reserve University Method for optical coherence tomography imaging with molecular contrast
7099358, Aug 05 2005 Santec Corporation Tunable laser light source
7113288, Jun 15 2001 Carl Zeiss Jena GmbH Numerical a posteriori dispersion compensation in PCI measurement signals and OCT A-scan signals with spatially variant correlation core
7113625, Oct 01 2004 U S PATHOLOGY LABS, INC System and method for image analysis of slides
7130320, Nov 13 2003 Mitutoyo Corporation External cavity laser with rotary tuning element
7139598, Apr 04 2002 VERALIGHT, INC Determination of a measure of a glycation end-product or disease state using tissue fluorescence
7142835, Sep 29 2003 SILICON LABORATORIES, INC Apparatus and method for digital image correction in a receiver
7148970, Oct 16 2001 The General Hospital Corporation Systems and methods for imaging a sample
7177027, May 17 2002 Japan Science and Technology Agency Autonomous ultra-short optical pulse compression, phase compensating and waveform shaping device
7190464, May 14 2004 VZN CAPITAL, LLC Low coherence interferometry for detecting and characterizing plaques
7230708, Dec 28 2000 LAPOTKO, TATIANA, MS Method and device for photothermal examination of microinhomogeneities
7231243, Oct 30 2000 The General Hospital Corporation Optical methods for tissue analysis
7236637, Nov 24 1999 GE Medical Systems Information Technologies, Inc.; GE MEDICAL SYSTEMS INFORMATION TECHNOLOGIES, INC Method and apparatus for transmission and display of a compressed digitized image
7242480, May 14 2004 CARDIOLUMEN, INC Low coherence interferometry for detecting and characterizing plaques
7267494, Feb 01 2005 II-VI Incorporated; MARLOW INDUSTRIES, INC ; EPIWORKS, INC ; LIGHTSMYTH TECHNOLOGIES, INC ; KAILIGHT PHOTONICS, INC ; COADNA PHOTONICS, INC ; Optium Corporation; Finisar Corporation; II-VI OPTICAL SYSTEMS, INC ; M CUBED TECHNOLOGIES, INC ; II-VI PHOTONICS US , INC ; II-VI DELAWARE, INC; II-VI OPTOELECTRONIC DEVICES, INC ; PHOTOP TECHNOLOGIES, INC Fiber stub for cladding mode coupling reduction
7272252, Jun 12 2002 Carl Zeiss Microscopy GmbH Automated system for combining bright field and fluorescent microscopy
7304798, Sep 03 2003 Fujitsu Limited Spectroscopic apparatus
7330270, Jan 21 2005 CARL ZEISS MEDITEC, INC Method to suppress artifacts in frequency-domain optical coherence tomography
7336366, Jan 20 2005 Duke University Methods and systems for reducing complex conjugate ambiguity in interferometric data
7342659, Jan 21 2005 CARL ZEISS MEDITEC, INC Cross-dispersed spectrometer in a spectral domain optical coherence tomography system
7355716, Jan 24 2002 GENERAL HOSPITAL CORPORATION THE Apparatus and method for ranging and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands
7355721, May 08 2003 D4D Technologies, LLC Optical coherence tomography imaging
7359062, Dec 09 2003 The Regents of the University of California High speed spectral domain functional optical coherence tomography and optical doppler tomography for in vivo blood flow dynamics and tissue structure
7366376, Sep 29 2004 The General Hospital Corporation System and method for optical coherence imaging
7382809, Feb 25 2005 Santec Corporation Tunable fiber laser light source
7391520, Jul 01 2005 CARL ZEISS MEDITEC, INC Fourier domain optical coherence tomography employing a swept multi-wavelength laser and a multi-channel receiver
7458683, Jun 16 2003 AMO Manufacturing USA, LLC Methods and devices for registering optical measurement datasets of an optical system
7530948, Feb 28 2005 University of Washington Tethered capsule endoscope for Barrett's Esophagus screening
7539530, Aug 22 2003 INFRAREDX, INC Method and system for spectral examination of vascular walls through blood during cardiac motion
7609391, Nov 23 2004 Optical lattice microscopy
7630083, Jan 24 2002 The General Hospital Corporation Apparatus and method for ranging and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands
7643152, Jan 24 2002 The General Hospital Corporation Apparatus and method for ranging and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands
7643153, Jan 24 2003 The General Hospital Corporation Apparatus and method for ranging and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands
7646905, Dec 23 2002 Qinetiq Limited Scoring estrogen and progesterone receptors expression based on image analysis
7649160, Feb 23 2005 LYNCEE TEC S A Wave front sensing method and apparatus
7664300, Feb 03 2005 STI Medical Systems, LLC Uterine cervical cancer computer-aided-diagnosis (CAD)
7733497, Oct 27 2003 General Hospital Corporation, The Method and apparatus for performing optical imaging using frequency-domain interferometry
7782464, May 12 2006 The General Hospital Corporation Processes, arrangements and systems for providing a fiber layer thickness map based on optical coherence tomography images
7805034, Jan 29 2008 Namiki Seimitsu Houseki Kabushiki Kaisha OCT probe for eliminating ghost images
20010036002,
20010047137,
20020016533,
20020024015,
20020048025,
20020048026,
20020052547,
20020057431,
20020064341,
20020076152,
20020085209,
20020086347,
20020091322,
20020093662,
20020109851,
20020122182,
20020122246,
20020140942,
20020158211,
20020161357,
20020163622,
20020168158,
20020172485,
20020183623,
20020188204,
20020196446,
20020198457,
20030001071,
20030013973,
20030023153,
20030026735,
20030028114,
20030030816,
20030043381,
20030053673,
20030067607,
20030082105,
20030097048,
20030108911,
20030120137,
20030135101,
20030137669,
20030164952,
20030165263,
20030171691,
20030174339,
20030199769,
20030216719,
20030220749,
20030236443,
20040002650,
20040039298,
20040054268,
20040072200,
20040075841,
20040076940,
20040077949,
20040085540,
20040086245,
20040100631,
20040100681,
20040110206,
20040126048,
20040126120,
20040133191,
20040150829,
20040150830,
20040152989,
20040165184,
20040166593,
20040189999,
20040212808,
20040239938,
20040246490,
20040246583,
20040254474,
20040263843,
20050018133,
20050018201,
20050035295,
20050036150,
20050046837,
20050057680,
20050057756,
20050059894,
20050065421,
20050075547,
20050083534,
20050119567,
20050128488,
20050165303,
20050171438,
20050190372,
20050254061,
20060033923,
20060093276,
20060103850,
20060146339,
20060155193,
20060164639,
20060171503,
20060184048,
20060193352,
20060244973,
20070013002,
20070019208,
20070038040,
20070070496,
20070076217,
20070086013,
20070086017,
20070091317,
20070188855,
20070223006,
20070236700,
20070258094,
20070291277,
20080002197,
20080007734,
20080049220,
20080094613,
20080094637,
20080097225,
20080097709,
20080100837,
20080152353,
20080154090,
20080204762,
20080265130,
20080308730,
20090011948,
20090196477,
20090273777,
20090290156,
20100086251,
20100094576,
20100150467,
CN1550203,
DE10351319,
DE19542955,
DE4105221,
DE4309056,
EP110201,
EP251062,
EP590268,
EP617286,
EP728440,
EP933096,
EP1426799,
FR2738343,
GB1257778,
GB2030313,
GB2209221,
GB2298054,
JP2002214127,
JP20030035659,
JP20040056907,
JP2007271761,
JP4135550,
JP4135551,
JP5509417,
JP6073405,
WO58766,
WO101111,
WO108579,
WO127679,
WO138820,
WO142735,
WO2053050,
WO2054027,
WO2084263,
WO236015,
WO237075,
WO238040,
WO3020119,
WO3046495,
WO3046636,
WO3052478,
WO3062802,
WO3105678,
WO1324051,
WO2004034869,
WO2004057266,
WO2004066824,
WO2004088361,
WO2004105598,
WO2005000115,
WO20050082225,
WO2005047813,
WO2005054780,
WO2005082225,
WO2006004743,
WO2006014392,
WO2006038876,
WO2006039091,
WO2006059109,
WO2006124860,
WO2006130797,
WO2007028531,
WO2007038787,
WO2007083138,
WO2007084995,
WO7900841,
WO9201966,
WO9216865,
WO9219865,
WO9219930,
WO9303672,
WO9533971,
WO9628212,
WO9732182,
WO9800057,
WO9801074,
WO9814132,
WO9835203,
WO9838907,
WO9846123,
WO9848838,
WO9848846,
WO9905487,
WO9944089,
WO9957507,
/////
Executed onAssignorAssigneeConveyanceFrameReelDoc
Jul 09 2004DEBOER, JOHANNES F The General Hospital CorporationASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS 0202440437 pdf
Jul 09 2004TEARNEY, GUILLERMO J The General Hospital CorporationASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS 0202440437 pdf
Jul 09 2004BOUMA, BRETT E The General Hospital CorporationASSIGNMENT OF ASSIGNORS INTEREST SEE DOCUMENT FOR DETAILS 0202440437 pdf
Dec 13 2007The General Hospital Corporation(assignment on the face of the patent)
Mar 27 2009The General Hospital CorporationUS GOVERNMENT - SECRETARY FOR THE ARMYCONFIRMATORY LICENSE SEE DOCUMENT FOR DETAILS 0230480762 pdf
Date Maintenance Fee Events
May 08 2015M1551: Payment of Maintenance Fee, 4th Year, Large Entity.
May 08 2019M1552: Payment of Maintenance Fee, 8th Year, Large Entity.
May 08 2023M1553: Payment of Maintenance Fee, 12th Year, Large Entity.


Date Maintenance Schedule
Nov 08 20144 years fee payment window open
May 08 20156 months grace period start (w surcharge)
Nov 08 2015patent expiry (for year 4)
Nov 08 20172 years to revive unintentionally abandoned end. (for year 4)
Nov 08 20188 years fee payment window open
May 08 20196 months grace period start (w surcharge)
Nov 08 2019patent expiry (for year 8)
Nov 08 20212 years to revive unintentionally abandoned end. (for year 8)
Nov 08 202212 years fee payment window open
May 08 20236 months grace period start (w surcharge)
Nov 08 2023patent expiry (for year 12)
Nov 08 20252 years to revive unintentionally abandoned end. (for year 12)